Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolism of encainide occurs in the liver and is polymorphically distributed according to the same genetic factor that determines the 4-hydroxylation of debrisoquine. Over 90% of patients are extensive metabolizers (EM) in whom the oral bioavailability of encainide is only 30% because of extensive first-pass metabolism. In EMs, elimination t1/2 is about 2.5 hours, with a systemic clearance of 1.8 l/min. The plasma concentrations of the major metabolites O-desmethyl-encainide (ODE) and 3-methoxy-O-desmethyl-encainide (3-MODE) are higher than those of encainide and have antiarrhythmic activity. The remaining patients (less than 10%) are poor metabolizers (PM), in whom the oral bioavailability is near 88% with an elimination t1/2 of 8-11 hours and a systemic clearance of 0.2 l/min. Encainide plasma concentrations are 10- to 20-fold higher than in EMs, but considerably less ODE and no 3-MODE is formed by the PMs. The conversion to the N-desmethyl-encainide (NDE) metabolite seems to be similar in both metabolizer groups, and plasma protein binding of encainide of 70-78% is also similar. During long-term treatment, the antiarrhythmic metabolites of encainide accumulate in the plasma, so that the relationships between the effect and plasma concentration on encainide, ODE, and 3-MODE are not always obvious. Minimally effective plasma concentrations appear to be approximately 300 ng/ml of encainide, 35 ng/ml of ODE, and 100 ng/ml of 3-MODE. Dose adjustment is necessary in patients with decreased kidney function, but not in patients with cirrhosis, in whom the plasma levels of metabolites appear to be comparable to those in normal subjects.
Cardiovasc Drugs Ther 1990 Jun
PMID:Pharmacokinetics and metabolism of encainide. 212 33

It has been demonstrated that serotonin (5-hydroxytryptamine; 5HT) can decrease portal vascular resistance in animals and could be a possible mediator for intestinal vasodilatation. Moreover, isolated mesenteric vein from portal hypertensive rats has been shown to be hyper-responsive to 5HT. Hence 5HT may play a role in the pathophysiology of the hyperkinetic syndrome observed in patients with portal hypertension. This hypothesis that serotonin might increase splanchnic blood flow, and hence portal pressure, led us to propose that 5HT receptor antagonists might decrease portal hypertension. We observed that acute administration of ketanserin, an antagonist of serotonin at 5HT2 receptors, significantly decreased portal pressure and portal-systemic collateral blood flow in patients with cirrhosis, whereas hepatic blood flow was not modified. Arterial pressure slightly decreased, while cardiac output was not affected by ketanserin. These findings were also observed during continuous administration of ketanserin. More recently, it has been shown that ritanserin, a more specific 5HT2 receptor antagonist, significantly decreased portal pressure in cirrhotic patients. Finally, in rats with portal hypertension, ketanserin as well as ritanserin produced significant reductions in portal pressure but did not modify portal tributory blood flow. In these portal hypertensive animals, 5HT2 antagonists may act on hepatocollateral vascular resistance. These studies confirm current evidence in favor of a role for the actions of serotonin via 5HT2 receptors in portal hypertension and add a new group of substances for its treatment.
Cardiovasc Drugs Ther 1990 Jan
PMID:Portal hypertension: serotonin and pathogenesis. 228 48

Pharmacokinetic data obtained after intravenous and single and repeat chronic oral dosing of indoramin in nine patients with liver cirrhosis are described. Median plasma clearance is 11.2 ml/min/kg. Terminal disposition half-life is prolonged after intravenous as well as acute and chronic oral dosing (9.1 versus 10.7 versus 12.2 h). Median volume of distribution is 11.2 L/kg. Bioavailability is increased with a wide range of distribution from 12.2 to 75.4%. There is a slight tendency of accumulation during twice daily oral dosing that cannot be explained by the degree of prolongation of half-life. The kinetics of the main metabolite, 6-hydroxyindoramin, are substantially comparable to the kinetics of indoramin with a ratio of 6-hydroxyindoramin/indoramin calculated from the area under plasma concentration-time curve of 0.3, which is within the range of normal. All data suggest that the changed pharmacokinetics are due to altered liver perfusion as would be expected from a substance with a plasma clearance in the magnitude of liver perfusion in normal volunteers. It seems likely that, in patients with liver cirrhosis, similar alpha 1 blocking effects may be achieved with lower doses than in patients with normal liver function.
J Cardiovasc Pharmacol 1986
PMID:Pharmacokinetics of indoramin and its metabolite 6-hydroxyindoramin after single and multiple doses to cirrhotic liver patients. 242 91

In hypoosmolar hyponatremia, vasopressin is commonly observed to be less than maximally suppressed. This is attributed to the presence of nonosmolar vasopressin stimuli. However, the exact relationship of nonsuppressed antidiuretic hormone to specific circulatory parameters is controversial. Therefore, in the present study, we examined this question in 100 hypoosmolar hyponatremic patients in the Department of Medicine. Despite plasma hypoosmolality, vasopressin was found to be measurable in 92% of patients. Seventy patients suffered from edematous disorders (congestive heart failure, cirrhosis) or volume contraction per se; in these patients we observed unequivocal, though indirect, evidence of advanced circulatory alterations. These were associated with hyponatremia and nonsuppressed vasopressin. However, the latter could not be related directly to a specific circulatory parameter such as mean arterial blood pressure, creatinine clearance, plasma renin activity (PRA), norepinephrine, or aldosterone. However, patients with nondetectable vasopressin (n = 8) differed significantly from those with high vasopressin concentrations (n = 8: PADH greater than 9 pg/ml); in the latter, pulse rate (104 +/- 3 vs. 82 +/- 5 beats/min), plasma urea concentration (90 +/- 5 vs. 32 +/- 5 mg/dl), plasma urate concentration (7.2 +/- 0.8 vs. 3.6 +/- 0.8 mg/dl), and PRA (36 +/- 7 vs. 9.5 +/- 4.6 ng AI/ml/h) were all significantly higher than in the former. It is concluded that, in hyponatremia, the relationship between circulatory impairment and vasopressin is complex.
J Cardiovasc Pharmacol 1986
PMID:Vasopressin in hyponatremia: what stimuli? 243 81

The effect of a synthetic atrial natriuretic peptide (h-ANP, 25 amino acids, Wy-47.663) on blood pressure, renal electrolyte excretion, plasma catecholamines, and plasma renin activity was studied in nine patients with cirrhosis of the liver and ascites. The peptide was infused intravenously at 24-h intervals for 2 h in groups of four patients each in two different doses (0.015 and 0.075 micrograms/kg/min or 0.06 and 0.3 micrograms/kg/min). A control experiment with the vehicle was performed in all patients. In three patients h-ANP (1 and 2 micrograms/kg i.v.) was administered as an intravenous bolus injection. Consistent falls in blood pressure were observed during h-ANP infusion only with the two higher doses. The two lower infused doses induced a consistent natriuresis; this renal response was abolished when the two larger doses were used. When given as a bolus, h-ANP had a natriuretic effect comparable to that of the two lower doses of infused h-ANP. Plasma catecholamines and plasma renin activity increased during infusion of the two higher doses of h-ANP. It thus appears that in patients with cirrhosis and ascites, the natriuretic effect of infused h-ANP decreases rather than increases when the doses are raised. Bolus administration of h-ANP may be less prone to trigger counterbalancing responses and side-effects.
J Cardiovasc Pharmacol 1988 Sep
PMID:Atrial natriuretic peptide administered as intravenous infusion or bolus injection to patients with liver cirrhosis and ascites. 246 99

Metabolism of nitrendipine occurs principally in the liver. Therefore, an alteration of pharmacokinetics has to be discussed in patients with hepatic impairment. To evaluate steady-state plasma concentrations and pharmacokinetics, a low dose of nitrendipine (5 mg/day for 3 weeks) was administered orally to patients with different chronic liver diseases (fatty liver, n = 3; chronic hepatitis, n = 2; and cirrhosis of the liver, n = 5). Nitrendipine plasma concentrations were analyzed by using a gas-liquid chromatography procedure. Twenty-two days after beginning the study, steady-state plasma concentrations were lower than 1.0 microgram/L in one patient without liver disease and in seven patients with chronic liver diseases, in contrast to three patients with alcoholic cirrhosis (5.5, 1.3, and 2.9 micrograms/L). The maximum concentration (Cmax) was 2.3 micrograms/L in the patient without liver disease and 8.3 +/- 3.9 micrograms/L in the hepatic patients. The elimination half-life was prolonged in three of five patients with cirrhosis of the liver (35, 67, and 43 h), whereas in the other patients the half-life was in a normal range (4.2-21.3 h). The area under the concentration-time curve (AUC) was enhanced in three patients with liver cirrhosis (387, 69, and 126 h/micrograms/L); in the other seven hepatic patients, results were normal (35-49 h/micrograms/L). There were no alterations observed in any patient in blood pressure and laboratory data. Oral administration of a low dose of nitrendipine resulted in slightly enhanced steady state plasma concentrations only in patients with advanced cirrhosis of the liver. The half-life, AUC, and bioavailability also seem to be altered only in a more severe state of liver disease.
J Cardiovasc Pharmacol 1988
PMID:Disposition of nitrendipine in patients with chronic liver diseases. 246 69

Nitrendipine [3-ethyl-5-methyl-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridine dicarboxylate] is a calcium antagonist with a dihydropyridine structure that has a great structural resemblance to nifedipine. Instead of a methyl group in position 3, it has an ethyl group and the NO2 group is in the meta instead of in the ortho position. These minor structural differences have a pronounced impact with respect to both the pharmacokinetics and pharmacodynamics of nitrendipine as compared to nifedipine. Based on equimolar plasma concentrations, nitrendipine is on average three times more potent than nifedipine with regard to the reduction of peripheral vascular resistance, arterial blood pressure, and increased leg blood flow. The terminal half-life is on average 8 h, and thus substantially longer than the terminal half-life of 2-3 h for nifedipine. Despite its almost complete absorption, bioavailability is on average 15-25% and shows great interindividual variability ranging from 7 to 40%. The systemic plasma clearance of the drug is on average 18 ml/min/kg and thus approaches the liver blood flow. In patients with liver cirrhosis, the half-life is prolonged to 19.6 h, the total plasma clearance is decreased by 50%, and the bioavailability is more than doubled to 54%. No data are available if liver disease alters the pharmacodynamic response of the drug. Kidney disease has some effect on the disposition of the drug. Systemic clearance is not changed but the terminal elimination half-life is slightly prolonged to 10.5 h. This increase in half-life is due to an increased volume of distribution. Bioavailability, which is 21.2%, is not grossly altered in renal failure.
J Cardiovasc Pharmacol 1988
PMID:Pharmacokinetics and pharmacodynamics of nitrendipine in healthy subjects and patients with kidney and liver disease. 246 76

Results of 287 transthoracoabdominal esophageal transections (Sugiura procedure), 125 transthoracic esophageal transections, 48 transabdominal esophageal transections, and 58 other nonshunting operations performed during the past 25 years were analyzed. Overall operative mortality rate was 5.0% (26/518); however, it was observed only in patients with liver cirrhosis (7.0%) and was higher in emergency cases (23.3%) and patients classified Child C (17.1%). Two hundred two patients died during the follow-up period, which lasted 24 years; 33 patients died of rebleeding, 89 of hepatic failure, 65 of hepatoma, and 35 of other causes. Cumulative survival rates of patients after non-shunting operations differed significantly according to the nature of the original diseases and the severity of liver damage. The cumulative survival rate at 10 years in patients with extrahepatic portal obstruction was 90.7%, 77.6% in idiopathic portal hypertension, and 33.0% in liver cirrhosis and at 20 years, 85.6%, 37.9%, and 8.1% respectively. The cumulative survival rate at 5 years in patients classified Child A was 88.7%, 77.7% in Child B, and 39.5% in Child C, and at 10 years, 73.4%, 45.3%, and 14.1%, respectively. Esophageal transection can be performed safely and is recommended in patients classified Child A or B. Patients in Child C should be treated by endoscopic sclerotherapy and other conservative measures.
J Thorac Cardiovasc Surg 1989 Nov
PMID:Twenty-five-year experiences with esophageal transection for esophageal varices. 281 21

A case is presented of hemopericardium and sudden death due to rupture of a solitary myocardial abscess in an elderly woman with cirrhosis and mild urosepsis. If suspected clinically, such myocardial abscesses may be detectable by noninvasive tomographic cardiac imaging.
Am J Cardiovasc Pathol 1988
PMID:Fatal hemopericardium due to ruptured solitary myocardial abscess unassociated with infective endocarditis. 321 8

An esophagovisceral anastomotic leak is a life-threatening postoperative complication, especially in the mediastinum. Of the 242 patients who underwent intrathoracic esophagogastric anastomosis for esophageal carcinoma (182 patients) and adenocarcinoma of the cardia (60 patients) between January 1980 and June 1985, 14 (5.8%) had esophageal anastomotic leakage and two died (0.8%). Various clinical and biologic parameters and aspects of operative technique were studied prospectively and analyzed statistically to identify possible factors responsible for leaks. Both bivariate and multivariate statistical analysis with logistic regression showed that the following clinical and biologic factors do not influence anastomotic leakage: tumor stage, the curative or palliative purpose of resection, neoplastic permeation of anastomotic margins, total protein concentration below 5 gm/dl, albumin concentration below 3 gm/dl, patient's age, diabetes, high blood pressure, cirrhosis of the liver, and cardiac, respiratory, or renal diseases. Technical factors, on the contrary, were statistically significant and of great clinical importance: manual as opposed to mechanical suturing (chi 2 = 8.8, p = 0.013) and single-layer as opposed to double-layer suturing (chi 2 = 9.9, p = 0.043). The level of the anastomosis was found to be a further statistically significant factor: The incidence of leakage was greater when the anastomosis was located between the azygos vein and the lower pulmonary vein (chi 2 = 15.5, p = 0.004) than above the azygos vein or below the lower pulmonary vein.
J Thorac Cardiovasc Surg 1988 Apr
PMID:Esophagovisceral anastomotic leak. A prospective statistical study of predisposing factors. 328 Aug 82


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